(A) Immunoblots of kinase substrates in the PI3K (Akt) and Ras (p38, Erk and eIF4E) pathways 2 h after treatment with vehicle, the Mek1 inhibitor UO126, the Mnk1 inhibitor CGP57380 or the PI3K inhibitor LY294002 (concentrations in µM are shown at the top). (B) Kinetics of viral growth (top) and translation (bottom) in mock- or inhibitor-treated U-118 cells infected with PVSRIPO. Progeny was quantified by plaque assay and viral translation was measured by immunoblot of the viral nonstructural proteins 2BC/2C. Viral propagation in mock- and UO126-treated cells was similar (data not shown). (C) PVSRIPO cytotoxicity in mock- or inhibitor-treated U-118 cells at the indicated intervals. (D) Photomicrographs of PVSRIPO-infected (MOI = 1) and vehicle (mock)- or CGP57380 (CGP; 30 μM)-treated U-118 cells at the indicated intervals.
2BC: Poliovirus protein 2BC; 2C: Poliovirus protein 2C; eIF: Eukaryotic initiation factor; MOI: Multiplicity of infection.
Reproduced with permission from [61].